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1.
J Appl Physiol (1985) ; 133(3): 679-688, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35952349

RESUMO

Low resting inspiratory capacity (IC) and low maximal inspiratory pressure (MIP) have previously been linked to exertional dyspnea, exercise limitation, and poor survival in chronic obstructive pulmonary disease (COPD). The interaction and relative contributions of these two related variables to important clinical outcomes are unknown. The objective of the current study was to examine the interaction between resting IC and MIP (both % predicted), exertional dyspnea, exercise capacity, and long-term survival in patients with COPD. Two hundred and eighty-five patients with mild to advanced COPD completed standard lung function testing and a cycle cardiopulmonary exercise test. Multiple regression determined predictors of the exertional dyspnea-ventilation slope and peak oxygen uptake (V̇o2peak). Cox regression determined predictors of 10-year mortality. IC was associated with the dyspnea-ventilation slope (standardized ß = -0.42, P < 0.001), whereas MIP was excluded from the regression model (P = 0.918). IC and MIP were included in the final model to predict V̇o2peak. However, the standardized ß was greater for IC (0.43) than MIP (0.22). After adjusting for age, sex, body mass index, cardiovascular risk, airflow obstruction, and diffusing capacity, resting IC was independently associated with 10-year all-cause mortality (hazard ratio = 1.25, confidence interval5%-95% = 1.16-1.34, P < 0.001), whereas MIP was excluded from the final model (all P = 0.829). Low resting IC was consistently linked to heightened dyspnea intensity, low V̇o2peak, and worse survival in COPD even after accounting for airway obstruction, inspiratory muscle strength, and diffusing capacity. These results support the use of resting IC as an important physiological biomarker closely linked to key clinical outcomes in COPD.NEW & NOTEWORTHY To our knowledge, this study is the first to show an independent association between low resting inspiratory capacity (IC) and, severe exertional dyspnea, exercise limitation, and increased mortality risk, after accounting for the severity of airway obstruction, inspiratory muscle strength, and diffusing capacity. These results support the use of resting IC as an important independent physiological biomarker closely linked to key clinical outcomes in COPD.


Assuntos
Obstrução das Vias Respiratórias , Doença Pulmonar Obstrutiva Crônica , Dispneia , Teste de Esforço/métodos , Tolerância ao Exercício/fisiologia , Humanos , Capacidade Inspiratória/fisiologia , Morbidade , Força Muscular
2.
Med Sci Sports Exerc ; 53(12): 2467-2476, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34649264

RESUMO

INTRODUCTION: Evaluation of the intensity and quality of activity-related dyspnea is potentially useful in people with chronic obstructive pulmonary disease (COPD). The present study sought to examine associations between qualitative dyspnea descriptors, dyspnea intensity ratings, dynamic respiratory mechanics, and exercise capacity during cardiopulmonary exercise testing (CPET) in COPD and healthy controls. METHODS: In this cross-sectional study, 261 patients with mild-to-very severe COPD (forced expiratory volume in 1 s, 62 ± 25%pred) and 94 age-matched controls (forced expiratory volume in 1 s, 114 ± 14%pred) completed an incremental cycle CPET to determine peak oxygen uptake (V˙O2peak). Throughout exercise, expired gases, operating lung volumes, and dyspnea intensity were assessed. At peak exercise, dyspnea quality was assessed using a modified 15-item questionnaire. RESULTS: Logistic regression analysis revealed that among 15 dyspnea descriptors, only those alluding to the cluster "unsatisfied inspiration" were consistently associated with an increased likelihood for both critical inspiratory mechanical constraint (end-inspiratory lung volume/total lung capacity ratio ≥0.9) during exercise and reduced exercise capacity (V˙O2peak < lower limit of normal) in COPD (odds ratio (95% confidence interval), 3.26 (1.40-7.60) and 3.04 (1.24-7.45), respectively; both, P < 0.05). Thus, patients reporting "unsatisfied inspiration" (n = 177 (68%)) had an increased relative frequency of critical inspiratory mechanical constraint and low exercise capacity compared with those who did not select this descriptor, regardless of COPD severity or peak dyspnea intensity scores. CONCLUSIONS: In patients with COPD, regardless of disease severity, reporting descriptors in the unsatisfied inspiration cluster complemented traditional assessments of dyspnea during CPET and helped identify patients with critical mechanical abnormalities germane to exercise intolerance.


Assuntos
Dispneia/fisiopatologia , Tolerância ao Exercício , Exercício Físico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Mecânica Respiratória , Estudos Retrospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários
3.
J Appl Physiol (1985) ; 127(4): 1107-1116, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369329

RESUMO

The mechanisms linking reduced diffusing capacity of the lung for carbon monoxide (DlCO) to dyspnea and exercise intolerance across the chronic obstructive pulmonary disease (COPD) continuum are poorly understood. COPD progression generally involves both DlCO decline and worsening respiratory mechanics, and their relative contribution to dyspnea has not been determined. In a retrospective analysis of 300 COPD patients who completed symptom-limited incremental cardiopulmonary exercise tests, we tested the association between peak oxygen-uptake (V̇o2), DlCO, and other resting physiological measures. Then, we stratified the sample into tertiles of forced expiratory volume in 1 s (FEV1) and inspiratory capacity (IC) and compared dyspnea ratings, pulmonary gas exchange, and respiratory mechanics during exercise in groups with normal and low DlCO [i.e.,

Assuntos
Dispneia/fisiopatologia , Tolerância ao Exercício/fisiologia , Exercício Físico/fisiologia , Capacidade Inspiratória/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Troca Gasosa Pulmonar/fisiologia , Descanso/fisiologia , Idoso , Obstrução das Vias Respiratórias/fisiopatologia , Teste de Esforço/métodos , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Capacidade de Difusão Pulmonar/métodos , Respiração , Testes de Função Respiratória/métodos , Mecânica Respiratória/fisiologia , Estudos Retrospectivos
4.
J Appl Physiol (1985) ; 125(2): 381-392, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29543134

RESUMO

Among patients with chronic obstructive pulmonary disease (COPD), those with the lowest maximal inspiratory pressures experience greater breathing discomfort (dyspnea) during exercise. In such individuals, inspiratory muscle training (IMT) may be associated with improvement of dyspnea, but the mechanisms for this are poorly understood. Therefore, we aimed to identify physiological mechanisms of improvement in dyspnea and exercise endurance following inspiratory muscle training (IMT) in patients with COPD and low maximal inspiratory pressure (Pimax). The effects of 8 wk of controlled IMT on respiratory muscle function, dyspnea, respiratory mechanics, and diaphragm electromyography (EMGdi) during constant work rate cycle exercise were evaluated in patients with activity-related dyspnea (baseline dyspnea index <9). Subjects were randomized to either IMT or a sham training control group ( n = 10 each). Twenty subjects (FEV1 = 47 ± 19% predicted; Pimax = -59 ± 14 cmH2O; cycle ergometer peak work rate = 47 ± 21% predicted) completed the study; groups had comparable baseline lung function, respiratory muscle strength, activity-related dyspnea, and exercise capacity. IMT, compared with control, was associated with greater increases in inspiratory muscle strength and endurance, with attendant improvements in exertional dyspnea and exercise endurance time (all P < 0.05). After IMT, EMGdi expressed relative to its maximum (EMGdi/EMGdimax) decreased ( P < 0.05) with no significant change in ventilation, tidal inspiratory pressures, breathing pattern, or operating lung volumes during exercise. In conclusion, IMT improved inspiratory muscle strength and endurance in mechanically compromised patients with COPD and low Pimax. The attendant reduction in EMGdi/EMGdimax helped explain the decrease in perceived respiratory discomfort despite sustained high ventilation and intrinsic mechanical loading over a longer exercise duration. NEW & NOTEWORTHY In patients with COPD and low maximal inspiratory pressures, inspiratory muscle training (IMT) may be associated with improvement of dyspnea, but the mechanisms for this are poorly understood. This study showed that 8 wk of home-based, partially supervised IMT improved respiratory muscle strength and endurance, dyspnea, and exercise endurance. Dyspnea relief occurred in conjunction with a reduced activation of the diaphragm relative to maximum in the absence of significant changes in ventilation, breathing pattern, and operating lung volumes.


Assuntos
Diafragma/fisiopatologia , Dispneia/fisiopatologia , Tolerância ao Exercício/fisiologia , Exercício Físico/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Músculos Respiratórios/fisiologia , Idoso , Exercícios Respiratórios/métodos , Teste de Esforço/métodos , Terapia por Exercício/métodos , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Força Muscular/fisiologia , Respiração , Testes de Função Respiratória/métodos
5.
Respir Physiol Neurobiol ; 252-253: 64-71, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29578103

RESUMO

This randomized, double-blind, crossover study aimed to determine if acute treatment with inhaled bronchodilators, by improving regional lung hyperinflation and ventilation distribution, would reduce dead space-to-tidal volume ratio (VD/VT); thus contributing to improved exertional dyspnea in COPD. Twenty COPD patients (FEV1 = 50 ±â€¯15% predicted; mean ±â€¯SD) performed pulmonary function tests and symptom-limited constant-work rate exercise at 75% peak-work rate (with arterialized capillary blood gases) after nebulized bronchodilator (BD; ipratropium 0.5mg + salbutamol 2.5 mg) or placebo (PL; normal saline). After BD versus PL: Functional residual capacity decreased by 0.4L (p = .0001). Isotime during exercise after BD versus PL (p < .05): dyspnea decreased: 1.2 ±â€¯1.9 Borg-units; minute ventilation increased: 3.8 ±â€¯5.5 L/min; IC increased: 0.24 ±â€¯0.28 L and VT increased 0.19 ±â€¯0.16 L. There was no significant difference in arterial CO2 tension or VD/VT, but alveolar ventilation increased by 3.8 ±â€¯5.5 L/min (p = .02). Post-BD improvements in respiratory mechanics explained 51% of dyspnea reduction at a standardized exercise time. Bronchodilator-induced improvements in respiratory mechanics were not associated with reduced wasted ventilation - a residual contributory factor to exertional dyspnea during exercise in COPD.


Assuntos
Broncodilatadores/uso terapêutico , Exercício Físico/fisiologia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Respiração/efeitos dos fármacos , Administração por Inalação , Estudos Cross-Over , Método Duplo-Cego , Dispneia/tratamento farmacológico , Dispneia/fisiopatologia , Teste de Esforço , Feminino , Volume Expiratório Forçado , Humanos , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Pletismografia Total , Capacidade de Difusão Pulmonar , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Troca Gasosa Pulmonar/efeitos dos fármacos , Espirometria
6.
Respir Physiol Neurobiol ; 247: 116-125, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28993264

RESUMO

This randomized, double-blind, crossover study examined the physiological rationale for using a dual long-acting bronchodilator (umeclidinium/vilanterol (UME/VIL)) versus its muscarinic-antagonist component (UME) as treatment for dyspnea and exercise intolerance in moderate COPD. After each 4-week treatment period, subjects performed pulmonary function and symptom-limited constant-work rate cycling tests with diaphragm electromyogram (EMGdi), esophageal (Pes), gastric (Pga) and transdiaphragmatic (Pdi) pressure measurements. Fourteen subjects completed the study. Both treatments improved spirometry and airway resistance. UME/VIL had larger increases in FEV1 (+0.14±0.23L, p<0.05) but no added reduction in lung hyperinflation compared with UME. Isotime during exercise after UME/VIL versus UME (p<0.05): "unpleasantness of breathing" fell 0.8±1.3 Borg units; mean expiratory flow and ventilation increased; Pdi and Pga decreased. There were no treatment differences in endurance time, breathing pattern, operating lung volumes, inspiratory neural drive (EMGdi) or respiratory muscle effort (Pes swings) during exercise. UME/VIL compared with UME was associated with reduced breathing unpleasantness reflecting improved airway and respiratory muscle function during exercise.


Assuntos
Broncodilatadores/uso terapêutico , Antagonistas Colinérgicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Idoso , Resistência das Vias Respiratórias/efeitos dos fármacos , Albuterol/uso terapêutico , Álcoois Benzílicos/uso terapêutico , Clorobenzenos/uso terapêutico , Estudos Cross-Over , Método Duplo-Cego , Dispneia/tratamento farmacológico , Dispneia/fisiopatologia , Eletromiografia , Feminino , Humanos , Inalação/efeitos dos fármacos , Inalação/fisiologia , Masculino , Pletismografia Total , Quinuclidinas/uso terapêutico , Testes de Função Respiratória , Músculos Respiratórios/efeitos dos fármacos , Músculos Respiratórios/fisiopatologia , Espirometria
8.
Expert Rev Respir Med ; 11(7): 549-563, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28548545

RESUMO

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) - an inflammatory disease of the airways, alveoli and lung microvasculature - is a leading cause of death worldwide. Smokers with milder airway obstruction constitute the majority of patients with this disease. Many studies have shown increased morbidity, activity-related dyspnea, exercise intolerance and mortality in such patients, compared with age-matched healthy populations. Clinical evaluation of symptomatic smokers with ostensibly mild airway obstruction poses a challenge in clinical practice as spirometry can obscure extensive heterogeneous pathophysiological impairment. Areas covered: A detailed review of the evidence for complex biological, physiological and radiological abnormalities in smokers who barely fit arbitrary spirometric criteria for COPD diagnosis. A brief discussion of the debate about current diagnostic spirometric criteria for COPD that can lead to diagnostic confusion and, in-some-instances, to inappropriate management. Finally, we provide a review of the clinical implications of these structural and functional abnormalities and try to build a solid rationale for earlier detection and effective, timely management. Expert commentary: The prevalence of mild COPD among smokers is high, yet under-diagnosis remains a major problem and there is lack of evidence-based management recommendations for this sub-population. Further tests beyond spirometry are useful in uncovering patho-physiological derangements that are clinically relevant.


Assuntos
Obstrução das Vias Respiratórias/fisiopatologia , Dispneia/fisiopatologia , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fumar/epidemiologia , Humanos , Prevalência , Espirometria
9.
Ann Am Thorac Soc ; 14(Supplement_1): S30-S39, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28398073

RESUMO

Low inspiratory capacity (IC), chronic dyspnea, and reduced exercise capacity are inextricably linked and are independent predictors of increased mortality in chronic obstructive pulmonary disease. It is no surprise, therefore, that a major goal of management is to improve IC by reducing lung hyperinflation to improve respiratory symptoms and health-related quality of life. The negative effects of lung hyperinflation on respiratory muscle and cardiocirculatory function during exercise are now well established. Moreover, there is growing appreciation that a key mechanism of exertional dyspnea in chronic obstructive pulmonary disease is critical mechanical constraints on tidal volume expansion during exercise when resting IC is reduced. Further evidence for the importance of lung hyperinflation comes from multiple studies, which have reported the clinical benefits of therapeutic interventions that reduce lung hyperinflation and increase IC. A reduced IC in obstructive pulmonary disease is further eroded by exercise and contributes to ventilatory limitation and dyspnea. It is an important outcome for both clinical and research studies.


Assuntos
Dispneia/fisiopatologia , Tolerância ao Exercício , Capacidade Inspiratória , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Exercício Físico , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Trabalho Respiratório
10.
COPD ; 14(3): 267-275, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28368706

RESUMO

Smokers with minor spirometric abnormalities can experience persistent activity-related dyspnea and exercise intolerance. Additional resting tests can expose heterogeneous physiological abnormalities, but their relevance and association with clinical outcomes remain uncertain. Subjects included sixty-two smokers (≥20 pack-years), with cough and/or dyspnea and minor airway obstruction [forced expiratory volume in one-second (FEV1) ≥80% predicted and >5th percentile lower limit of normal (LLN) (i.e., z-score >-1.64) using the 2012-Global Lung Function Initiative equations]. They underwent spirometry, plethysmography, oscillometry, single-breath nitrogen washout, and symptom-limited incremental cycle exercise tests. Thirty-two age-matched nonsmoking controls were also studied. Thirty-three (53%) of smokers had chronic obstructive pulmonary disease by LLN criteria. In smokers [n = 62; age 65 ± 11 years; smoking history 43 ± 19 pack-years; post-bronchodilator FEV1 z-score -0.60 ± 0.72 and FEV1/FVC z-score -1.56 ± 0.87 (mean ± SD)] versus controls, peak oxygen uptake (̇VO2) was 21 ± 7 vs. 32 ± 9 ml/kg/min, and dyspnea/̇VO2 slopes were elevated (both p < 0.0001). Smokers had evidence of peripheral airway dysfunction and maldistribution of ventilation when compared to controls. In smokers versus controls: lung diffusing capacity for carbon monoxide (DLCO) was 85 ± 22 vs. 105 ± 17% predicted, and residual volume (RV)/total lung capacity (TLC) was 36 ± 8 vs. 31 ± 6% (both p < 0.01). The strongest correlates of peak ̇VO2 were DLCO% predicted (r = 0.487, p < 0.0005) and RV/TLC% (r = -0.389, p = 0.002). DLCO% predicted was also the strongest correlate of dyspnea/̇VO2 slope (r = -0.352, p = 0.005). In smokers with mild airway obstruction, associations between resting tests of mechanics and pulmonary gas exchange and exercise performance parameters were weak, albeit consistent. Among these, DLCO showed the strongest association with important outcomes such as dyspnea and exercise intolerance measured during standardized incremental exercise tests.


Assuntos
Obstrução das Vias Respiratórias/fisiopatologia , Tolerância ao Exercício/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Descanso/fisiologia , Fumar/fisiopatologia , Idoso , Obstrução das Vias Respiratórias/complicações , Estudos de Casos e Controles , Tosse/etiologia , Dispneia/etiologia , Dispneia/fisiopatologia , Teste de Esforço , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Capacidade de Difusão Pulmonar , Doença Pulmonar Obstrutiva Crônica/complicações , Volume Residual , Fumar/efeitos adversos , Capacidade Vital
11.
Eur Respir Rev ; 25(141): 333-47, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27581832

RESUMO

Activity-related dyspnoea is often the most distressing symptom experienced by patients with chronic obstructive pulmonary disease (COPD) and can persist despite comprehensive medical management. It is now clear that dyspnoea during physical activity occurs across the spectrum of disease severity, even in those with mild airway obstruction. Our understanding of the nature and source of dyspnoea is incomplete, but current aetiological concepts emphasise the importance of increased central neural drive to breathe in the setting of a reduced ability of the respiratory system to appropriately respond. Since dyspnoea is provoked or aggravated by physical activity, its concurrent measurement during standardised laboratory exercise testing is clearly important. Combining measurement of perceptual and physiological responses during exercise can provide valuable insights into symptom severity and its pathophysiological underpinnings. This review summarises the abnormal physiological responses to exercise in COPD, as these form the basis for modern constructs of the neurobiology of exertional dyspnoea. The main objectives are: 1) to examine the role of cardiopulmonary exercise testing (CPET) in uncovering the physiological mechanisms of exertional dyspnoea in patients with mild-to-moderate COPD; 2) to examine the escalating negative sensory consequences of progressive respiratory impairment with disease advancement; and 3) to build a physiological rationale for individualised treatment optimisation based on CPET.


Assuntos
Dispneia/etiologia , Teste de Esforço , Exercício Físico , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Respiração , Dispneia/diagnóstico , Dispneia/fisiopatologia , Humanos , Valor Preditivo dos Testes , Prognóstico , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/terapia , Músculos Respiratórios/fisiopatologia , Fatores de Risco
12.
Eur Respir J ; 48(3): 694-705, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27492828

RESUMO

Dyspnoea and activity limitation can occur in smokers who do not meet spirometric criteria for chronic obstructive pulmonary disease (COPD) but the underlying mechanisms are unknown.Detailed pulmonary function tests and sensory-mechanical relationships during incremental exercise with respiratory pressure measurements and diaphragmatic electromyography (EMGdi) were compared in 20 smokers without spirometric COPD and 20 age-matched healthy controls.Smokers (mean±sd post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity 75±4%, mean±sd FEV1 104±14% predicted) had greater activity-related dyspnoea, poorer health status and lower physical activity than controls. Smokers had peripheral airway dysfunction: higher phase-III nitrogen slopes (3.8±1.8 versus 2.6±1.1%·L(-1)) and airway resistance (difference between airway resistance measured at 5 Hz and 20 Hz 19±11 versus 12±7% at 5 Hz) than controls (p<0.05). Smokers had significantly (p<0.05) lower peak oxygen uptake (78±40 versus 107±45% predicted) and ventilation (61±26 versus 97±29 L·min(-1)). Exercise ventilatory requirements, operating lung volumes and cardio-circulatory responses were similar. However, submaximal dyspnoea ratings, resistive and total work of breathing were increased in smokers compared with controls (p<0.05); diaphragmatic effort (transdiaphragmatic pressure/maximumal transdiaphragmatic pressure) and fractional inspiratory neural drive to the diaphragm (EMGdi/maximal EMGdi) were also increased (p<0.05) mainly reflecting the reduced denominator.Symptomatic smokers at risk for COPD had greater exertional dyspnoea and lower exercise tolerance compared with healthy controls in association with greater airways resistance, contractile diaphragmatic effort and fractional inspiratory neural drive to the diaphragm.


Assuntos
Dispneia/fisiopatologia , Tolerância ao Exercício/fisiologia , Volume Expiratório Forçado , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Adulto , Idoso , Índice de Massa Corporal , Estudos Transversais , Diafragma/fisiopatologia , Eletromiografia , Teste de Esforço , Feminino , Humanos , Inalação , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Oxigênio/química , Fenótipo , Respiração , Testes de Função Respiratória , Risco , Fumar , Espirometria , Capacidade Vital
13.
COPD ; 13(4): 416-24, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27077955

RESUMO

Severity of resting functional impairment only partially predicts the increased risk of death in chronic obstructive pulmonary disease (COPD). Increased ventilation during exercise is associated with markers of disease progression and poor prognosis, including emphysema extension and pulmonary vascular impairment. Whether excess exercise ventilation would add to resting lung function in predicting mortality in COPD, however, is currently unknown. After an incremental cardiopulmonary exercise test, 288 patients (forced expiratory volume in one second ranging from 18% to 148% predicted) were followed for a median (interquartile range) of 57 (47) months. Increases in the lowest (nadir) ventilation to CO2 output (VCO2) ratio determined excess exercise ventilation. Seventy-seven patients (26.7%) died during follow-up: 30/77 (38.9%) deaths were due to respiratory causes. Deceased patients were older, leaner, had a greater co-morbidity burden (Charlson Index) and reported more daily life dyspnea. Moreover, they had poorer lung function and exercise tolerance (p < 0.05). A logistic regression analysis revealed that ventilation/VCO2 nadir was the only exercise variable that added to age, body mass index, Charlson Index and resting inspiratory capacity (IC)/total lung capacity (TLC) ratio to predict all-cause and respiratory mortality (p < 0.001). Kaplan-Meier analyses showed that survival time was particularly reduced when ventilation/VCO2 nadir > 34 was associated with IC/TLC ≤ 0.34 or IC/TLC ≤ 0.31 for all-cause and respiratory mortality, respectively (p < 0.001). Excess exercise ventilation is an independent prognostic marker across the spectrum of COPD severity. Physiological abnormalities beyond traditional airway dysfunction and lung mechanics are relevant in determining the course of the disease.


Assuntos
Exercício Físico/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ventilação Pulmonar/fisiologia , Fatores Etários , Idoso , Índice de Massa Corporal , Dióxido de Carbono , Causas de Morte , Comorbidade , Dispneia/etiologia , Teste de Esforço , Tolerância ao Exercício , Feminino , Seguimentos , Volume Expiratório Forçado , Humanos , Capacidade Inspiratória , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mortalidade , Pletismografia Total , Capacidade de Difusão Pulmonar , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/mortalidade , Volume Residual , Espirometria , Taxa de Sobrevida , Capacidade Pulmonar Total
14.
Expert Rev Respir Med ; 10(7): 823-34, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27115291

RESUMO

INTRODUCTION: Activity-related breathlessness is often the dominant symptom in patients with chronic obstructive pulmonary disease (COPD) and usually persists despite optimal medical therapy. Currently, our inability to meaningfully alter the pathophysiology of the underlying disease means that we must focus our attention on relieving this distressing symptom so as to improve exercise tolerance and quality of life. AREAS COVERED: The current review examines the neurobiology of breathlessness and constructs a solid physiological rationale for amelioration of this distressing symptom. We will examine the efficacy of interventions which: 1) reduce the increased central drive to breathe (opioids); 2) improve the respiratory system's ability to appropriately respond to this increased demand (bronchodilators); and 3) address the important affective dimension of breathlessness (anxiolytics). Expert commentary: Advances in our understanding of the mechanisms of activity-related breathlessness in COPD, and its measurement in the clinical domain, now set the stage for the development of effective management strategies on an individual patient basis.


Assuntos
Dispneia/tratamento farmacológico , Dispneia/etiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Ansiolíticos/uso terapêutico , Broncodilatadores/uso terapêutico , Dispneia/psicologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
15.
J Pain Symptom Manage ; 52(1): 54-63, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26975626

RESUMO

CONTEXT: Breast cancer survivors often experience activity-related dyspnea and exercise intolerance, but the underlying mechanisms remain unknown. OBJECTIVES: We evaluated physiological contributors to reduced peak oxygen uptake (VO2), with particular attention to the role of respiratory impairment. METHODS: We compared symptom assessments, respiratory and peripheral muscle strength, pulmonary function, and ventilatory responses to symptom-limited incremental treadmill exercise in 29 women who had survived breast cancer and 29 age-matched healthy controls. RESULTS: Peak VO2 was reduced more than 20%, on average, in the cancer group compared with controls (P < 0.001). Slopes of dyspnea intensity ratings over ventilation or VO2 were >50% greater in the cancer group compared to controls (P < 0.05). Women with breast cancer had lower lung diffusing capacity for carbon monoxide (DLCO), respiratory and limb muscle strength, and ventilatory thresholds during exercise compared with controls (all P < 0.05). During exercise, indices of ventilatory efficiency were similar to controls, but inspiratory capacity (IC) was lower and breathing pattern was more rapid and shallow in the cancer group (P < 0.05). The lower peak VO2 in the cancer group was associated with greater dyspnea intensity, and lower DLCO, IC and ventilatory threshold (all P < 0.05). CONCLUSION: Breast cancer survivors had greater peripheral and respiratory muscle weakness, greater reduction of IC, impaired lung diffusion, and evidence of deconditioning compared with controls. Exercise intolerance was multifactorial and correlated well with the combination of these factors as well as with exertional dyspnea. Individualized physiological testing in breast cancer survivors can identify important contributors to exercise intolerance which can be targeted for treatment.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Dispneia/fisiopatologia , Tolerância ao Exercício/fisiologia , Respiração , Neoplasias da Mama/fisiopatologia , Monóxido de Carbono/metabolismo , Estudos de Casos e Controles , Dispneia/etiologia , Teste de Esforço , Extremidades/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Debilidade Muscular/fisiopatologia , Músculo Esquelético/fisiopatologia , Músculos Respiratórios/fisiopatologia , Espirometria
16.
Am J Respir Crit Care Med ; 193(3): 299-309, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26407036

RESUMO

RATIONALE: The mechanisms underlying dyspnea in interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD) are unknown. OBJECTIVES: To examine whether the relationship between inspiratory neural drive to the diaphragm and exertional dyspnea intensity is different in ILD and COPD, given the marked differences in static respiratory mechanics between these conditions. METHODS: We compared sensory-mechanical relationships in patients with ILD, patients with COPD, and healthy control subjects (n = 16 each) during incremental cycle exercise with diaphragmatic electromyography (EMGdi) and respiratory pressure measurements. MEASUREMENTS AND MAIN RESULTS: In patients with mild to moderate ILD or COPD with similarly reduced inspiratory capacity, the peak oxygen uptake, work rate, and ventilation were lower (P < 0.05) than in healthy control subjects. EMGdi expressed as a percentage of the maximum (EMGdi/EMGdi,max), respiratory effort (esophageal pressure expressed as percentage of the maximum), and ventilation were higher (P < 0.05) at rest and during exercise in both patients with ILD and patients with COPD than in control subjects. Each of these measurements was similar in the ILD and COPD groups. A Vt inflection and critically reduced inspiratory reserve volume occurred at a lower (P < 0.05) ventilation in the ILD and COPD groups than in control subjects. Patients with ILD had greater diaphragmatic activity, whereas patients with COPD had greater expiratory muscle activity. The relationship between dyspnea intensity and EMGdi/EMGdi,max during exercise was similar in all three groups. In ILD and COPD, descriptors alluding to inspiratory difficulty were selected more frequently, with a greater disparity between EMGdi/EMGdi,max and Vt. CONCLUSIONS: Disease-specific differences in mechanics and respiratory muscle activity did not influence the key association between dyspnea intensity and inspiratory neural drive to the diaphragm.


Assuntos
Dispneia/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Estudos Transversais , Diafragma/fisiopatologia , Eletromiografia , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Am J Respir Crit Care Med ; 191(12): 1384-94, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25826478

RESUMO

RATIONALE: Several studies in mild chronic obstructive pulmonary disease (COPD) have shown a higher than normal ventilatory equivalent for carbon dioxide ([Formula: see text]e/[Formula: see text]co2) during exercise. Our objective was to examine pulmonary gas exchange abnormalities and the mechanisms of high [Formula: see text]e/[Formula: see text]co2 in mild COPD and its impact on dyspnea and exercise intolerance. METHODS: Twenty-two subjects (11 patients with GOLD [Global Initiative for Chronic Obstructive Lung Disease] grade 1B COPD, 11 age-matched healthy control subjects) undertook physiological testing and a symptom-limited incremental cycle exercise test with arterial blood gas collection. MEASUREMENTS AND MAIN RESULTS: Patients (post-bronchodilator FEV1: 94 ± 10% predicted; mean ± SD) had evidence of peripheral airway dysfunction and reduced peak oxygen uptake compared with control subjects (80 ± 18 vs. 113 ± 24% predicted; P<0.05). Arterial blood gases were within the normal range and effective alveolar ventilation was not significantly different from control subjects throughout exercise. The alveolar-arterial O2 tension gradient was elevated at rest and throughout exercise in COPD (P<0.05). [Formula: see text]e/[Formula: see text]co2, dead space to tidal volume ratio (Vd/Vt), and arterial to end-tidal CO2 difference were all higher (P<0.05) in patients with COPD than in control subjects during exercise. In patients with COPD versus control subjects, there was significant dynamic hyperinflation and greater tidal volume constraints (P<0.05). Standardized dyspnea intensity ratings were also higher (P<0.05) in patients with COPD versus control subjects in association with higher ventilatory requirements. Within all subjects, Vd/Vt correlated with the [Formula: see text]e/[Formula: see text]co2 ratio during submaximal exercise (r=0.780, P<0.001). CONCLUSIONS: High Vd/Vt was the most consistent gas exchange abnormality in smokers with only mild spirometric abnormalities. Compensatory increases in minute ventilation during exercise maintained alveolar ventilation and arterial blood gas homeostasis but at the expense of earlier dynamic mechanical constraints, greater dyspnea, and exercise intolerance in mild COPD.


Assuntos
Dispneia/etiologia , Teste de Esforço/estatística & dados numéricos , Exercício Físico , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Troca Gasosa Pulmonar/fisiologia , Estudos Transversais , Dispneia/sangue , Dispneia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oximetria , Doença Pulmonar Obstrutiva Crônica/sangue
19.
Respir Physiol Neurobiol ; 205: 129-39, 2015 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25447683

RESUMO

To examine the effect of age-related respiratory function impairment on exertional dyspnea, we compared ventilatory and perceptual responses to incremental exercise under control (CTRL) and added dead space (DS) loading conditions in healthy fit older (55-79 years) and younger (20-39 years) men. Older individuals had higher ventilatory equivalents for CO2 throughout exercise (p<0.05) suggesting greater ventilatory inefficiency but operating lung volumes were similar compared to younger individuals. With added DS compared to CTRL, both groups similarly increased tidal volume (by 0.3-0.6 L) and ventilation (by 8-13 L/min) at submaximal work rates (each p<0.05). At peak exercise with DS, both groups failed to further increase ventilation and had small reductions in peak work rate (p<0.05). Increases in dyspnea intensity ratings with the addition of DS were similar at standardized submaximal work rates in older and younger groups. We conclude that, despite differences in ventilatory efficiency, the respiratory-mechanical and sensory responses to added chemostimulation during exercise were similar in fit older and younger individuals.


Assuntos
Aptidão Física/fisiologia , Ventilação Pulmonar/fisiologia , Adulto , Fatores Etários , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Espaço Morto Respiratório/fisiologia , Mecânica Respiratória/fisiologia , Adulto Jovem
20.
Chest ; 147(5): 1235-1245, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25393126

RESUMO

BACKGROUND: Smokers with persistent cough and sputum production (chronic bronchitis [CB]) represent a distinct clinical phenotype, consistently linked to negative clinical outcomes. However, the mechanistic link between physiologic impairment, dyspnea, and exercise intolerance in CB has not been studied, particularly in those with mild airway obstruction. We, therefore, compared physiologic abnormalities during rest and exercise in CB to those in patients without symptoms of mucus hypersecretion (non-CB) but with similar mild airway obstruction. METHODS: Twenty patients with CB (≥ 3 months cough/sputum in 2 successive years), 20 patients without CB but with GOLD (Global Initiative for Chronic Obstructive Lung Disease) grade IB COPD, and 20 age- and sex-matched healthy control subjects underwent detailed physiologic testing, including tests of small airway function and a symptom-limited incremental cycle exercise test. RESULTS: Patients with CB (mean ± SD postbronchodilator FEV1, 93% ± 12% predicted) had greater chronic activity-related dyspnea, poorer health-related quality of life, and reduced habitual physical activity compared with patients without CB and control subjects (all P < .05). The degree of peripheral airway dysfunction and pulmonary gas trapping was comparable in both patient groups. Peak oxygen uptake was similarly reduced in patients with CB and those without compared with control subjects (% predicted ± SD, 70 ± 26, 71 ± 29 and 106 ± 43, respectively), but those with CB had higher exertional dyspnea ratings and greater respiratory mechanical constraints at a standardized work rate than patients without CB (P < .05). CONCLUSIONS: Patients with CB reported greater chronic dyspnea and activity restriction than patients without CB and with similar mild airway obstruction. The CB group had greater dynamic respiratory mechanical impairment and dyspnea during exercise than patients without CB, which may help explain some differences in important patient-centered outcomes between the groups.


Assuntos
Bronquite Crônica/complicações , Bronquite Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Idoso , Bronquite Crônica/genética , Estudos Transversais , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Doença Pulmonar Obstrutiva Crônica/classificação , Índice de Gravidade de Doença
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